PPAR γ/TLR4/TGF-β1 axis mediates the protection effect of erythropoietin on cyclosporin A-induced chronic nephropathy in rat

Liu, Bin; Tan, Ping-Heng

doi:10.1080/0886022x.2020.1729188

Cited by 13 publications

(7 citation statements)

References 27 publications

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“…As our results unveiled, the contents of SCr, BUN, and mALB were clearly elevated after silencing of PPARc. In line with this finding, when PPARc is inhibited, serum levels of SCr and BUN are elevated, and renal function is damaged in rats with chronic nephropathy [29]. In the present study, there was obvious renal interstitial fibrosis in the renal tissue of HN rats, while the degree of renal interstitial fibrosis was clearly aggravated by silencing of PPARc.…”

Section: Discussionsupporting

confidence: 87%

microRNA-199a downregulation alleviates hyperuricemic nephropathy via the PPARγ/β-catenin axis

Chen

Deng

et al. 2021

Journal of Receptors and Signal Transduction

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Hyperuricemia always develops into hyperuricemic nephropathy (HN). The role of microRNA (miR) in HN is less studied. We aimed to discuss the role of miR-199a in HN. The expression of miR-199a and PPARc in renal tissues of HN rats was detected. The targeting relation between miR-199a and PPARc was verified. The contents of SCr, UA, BUN, and mALB, renal injury-relevant biomarkers were detected, and the pathological changes of renal tissue and renal interstitial fibrosis were observed by histological staining. After miR-199a and PPARc knockdown, the contents of SCr, BUN, and mALB and renal interstitial fibrosis were estimated. Collectively, overexpression of miR-199a aggravated the renal injury in HN rats. By contrast, inhibition of miR-199a weakened renal injury, as evidenced by decreased contents of SCr, UA, BUN, and mALB, and mitigated renal interstitial fibrosis. miR-199a targeted PPARc. Silencing of PPARc upregulated the levels of downstream genes of b-catenin and the contents of SCr, UA, BUN, and mALB and deteriorated renal interstitial fibrosis. Moreover, the silencing of PPARc blocked the alleviative effects of miR-199a inhibitor on the renal injury. Overall, miR-199a targets PPARc and activates the b-catenin pathway, thus aggravating HN, which might provide a future target for the treatment of HN.

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Section: Discussionsupporting

confidence: 87%

microRNA-199a downregulation alleviates hyperuricemic nephropathy via the PPARγ/β-catenin axis

Chen

Deng

et al. 2021

Journal of Receptors and Signal Transduction

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“…There was degeneration with exfoliation of some cells inside the lumen in the D.C.T and the peritubular capillaries were congested and extravasated. Liu and Tan (2020) reported that in cyclosporin A treated group there was marked vacuolar degeneration, atrophy, necrosis and exfoliation of kidney tubules, interstitial fibrosis, glomerular atrophy, and vascular congestion. Also, Al-Sa'aidi et al (2019) found that cyclosporine caused obvious atrophy of glomeruli, necrosis of Bowman capsule lining, cystic dilation of renal convoluted tubules and necrosis of their lining.…”

Section: Discussionmentioning

confidence: 98%

Experimental study of renal toxicity of cyclosporine and the ameliorative effect of N-acetylecysteine in albino rat

Abdelkader

Hilal

Torky

et al. 2021

Ain Shams Journal of Forensic Medicine and Clinical Toxicology

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Introduction: Cyclosporine A (CsA) is considered powerful immunosuppressive drug which has improved the quality of life and survival rate of transplant patients and also used in autoimmune diseases. However, its use is limited by many side effects mainly nephrotoxicity. NAC is an antioxidant found to reduce CsA toxicity. Aim of the work: The study aims to determine the effect of exposure to cyclosporine on the kidney and to investigate the protective role of NAC. Methods: the study conducted on 50 adult male albino rats for 4 weeks, divided into 5 groups, group A the negative control group, group B the olive oil group (0.5 ml/d orally), group C the cyclosporine group (25mg/kg/d orally), group D the NAC group (600mg/kg/d orally) and group E the cyclosporine+NAC group. At the end of the study the evaluation was done by biochemical analysis and histopathology. Results: cyclosporine significantly affects the kidney by morphological changes in the form of dilatation of urinary space with congestion and lobulation of glomerullar capillaries in the renal corpusle. Proximal convoluted tubules showed degeneration of their cells with irregularity and destruction of brush border. Degeneration of distal convoluted tubules with exfoliation of some cells inside the lumen and the peritubular capillaries were congested and extravasated. Also cyclosporine affects the kidney by increasing serum urea and creatinine levels, while coadministration of NAC with cyclosporine attenuate its effects. Conclusion: cyclosporine causes renal injury through oxidative stress and NAC as an antioxidant attenuates but not fully protect against cyclosporine induced injuries.

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“…(4) Ombuin + T0070907 group ( n = 10), in which rats were received 1 mg/kg/day T0070907 intraperitoneally based on the treatment of Ombuin group. The doses of T0070907 used in the current experiments were determined previously (Liu & Tan, 2020). (5) T0070907 group ( n = 10), in which rats were intraperitoneally injected with 1 mg/kg/day T0070907.…”

Section: Methodsmentioning

confidence: 99%

Ombuin ameliorates diabetic nephropathy in rats by anti‐inflammation and antifibrosis involving Notch 1 and PPAR γ signaling pathways

Liu

Deng

Tan

2022

Drug Development Research

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Diabetic nephropathy (DN) is a common complication of diabetes and it is urgent to develop effective therapies for DN. In this study, high‐sucrose and high‐fat diet combined with streptozotocin was used to induce DN in rats to observe the effects of natural flavonoid ombuin on renal function, inflammation, and interstitial fibrosis. Immunohistochemistry and western blotting analysis were used to detect protein expression levels. Results showed that ombuin significantly improved renal function and pathological injury, inhibited accumulation of advanced glycation end‐products, suppressed the release of inflammatory cytokines, and improved renal interstitial fibrosis in DN rats. Ombuin also significantly downregulated the expressions of transforming growth factor beta1 (TGF‐β1), connective tissue growth factor (CTGF), fibronectin (FN), p65, phosphorylated (p)‐p65, Cleaved‐Notch 1, and hairy and enhancer of split 1 (Hes 1), and upregulated the expression of peroxisome proliferator‐activated receptor γ (PPAR γ). When PPAR γ activity was inhibited by T0070907, the effects of ombuin on improving DN were significantly reversed, and the expressions of TGF‐β1, FN, CTGF, p‐p65, and p65 increased, while the expressions of Cleaved‐Notch 1 and Hes 1 were not significantly affected. These results suggest that ombuin may activate PPAR γ to exert anti‐inflammatory and antifibrotic effects by inhibiting Notch 1 activity in DN. It is also possible that ombuin acts on these two independent signal pathways synchronously.

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PPAR γ/TLR4/TGF-β1 axis mediates the protection effect of erythropoietin on cyclosporin A-induced chronic nephropathy in rat

Cited by 13 publications

References 27 publications

microRNA-199a downregulation alleviates hyperuricemic nephropathy via the PPARγ/β-catenin axis

microRNA-199a downregulation alleviates hyperuricemic nephropathy via the PPARγ/β-catenin axis

Experimental study of renal toxicity of cyclosporine and the ameliorative effect of N-acetylecysteine in albino rat

Ombuin ameliorates diabetic nephropathy in rats by anti‐inflammation and antifibrosis involving Notch 1 and PPAR γ signaling pathways

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